Glucocorticoids (GCs) are often used for the therapy of a variety of chronic autoimmune diseases because of their ability to simultaneously block both the innate and adaptive immune response. Studies over the last 10 years or so by the present inventors and other research groups have shown that some of the inflammatory effects of GCs on the innate immune response are mediated by a protein called Annexin-1 (Anx-A1). This protein has been proven to exert a homeostatic control over a number of cell types including neutrophils, macrophages and endothelial cells. However, one aspect that has always been neglected is the role of Anx-A1 in the adaptive immune response. This is surprising considering that Anx-A1 has been proposed as one of the second messengers of the pharmacological effects of GCs.
The present inventors have previously shown that Anx-A1 plays a homeostatic role in T cells by modulating the strength of T cell receptor (TCR) signaling (D'Acquisto et al., Blood 109: 1095-1102, 2007).
Furthermore, the inventors have shown that high levels of Anx-A1 lower the threshold of T cell activation and favour the differentiation into Th1 cells, whereas Anx-A1 deficient mice show impaired T cell activation and increased differentiation into Th2 cells (D'Acquisto et al., Eur. J. Immunol. 37: 3131-3142, 2007).
WO 2005/027965 describes the discovery of a mechanism by which apoptotic neutrophils deliver anti-inflammatory signals to dendritic cells and identifies an antibody that interferes with this process.